Activation of platelet-derived growth factor receptor alpha contributes to liver fibrosis.
Activation of platelet-derived growth factor receptor alpha contributes to liver fibrosis.
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DOI：
10.1371/journal.pone.0092925
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Campbell JS
中科院分区：
文献类型：
--
作者：
Hayes BJ;Riehle KJ;Shimizu-Albergine M;Bauer RL;Hudkins KL;Johansson F;Yeh MM;Mahoney WM Jr;Yeung RS;Campbell JS
慢性肝损伤会导致纤维化、肝硬变和肝功能丧失。在美国，肝硬变是第12大死因，也是发展为肝癌的主要危险因素。肝纤维化和肝硬变是由肝星状细胞(HSCs)激活引起的，HSCs是肝脏中主要的胶原生成细胞类型。在这里，我们发现血小板衍生生长因子受体α(PDGFRα)在人的HSC中表达，并且在人类肝病中表达升高。我们利用绿色荧光蛋白报告基因α在小鼠肝脏疾病中的作用进行了评估，发现小鼠肝干细胞表达PDGFRα，并且在四氯化碳诱导的肝损伤和肝纤维化过程中表达上调。这种纤维化反应在PDGFFRα杂合子小鼠中降低，这与肝纤维化需要上调和激活PDGFFRα的假设一致。这些结果表明，PDGFRα的表达在人和小鼠肝损伤的纤维化反应中起重要作用，并提示阻断肝干细胞中PDGFFRα特异的信号通路可能为慢性肝病患者提供治疗益处。
Chronic liver injury leads to fibrosis, cirrhosis, and loss of liver function. Liver cirrhosis is the 12th leading cause of death in the United States, and it is the primary risk factor for developing liver cancer. Fibrosis and cirrhosis result from activation of hepatic stellate cells (HSCs), which are the primary collagen producing cell type in the liver. Here, we show that platelet-derived growth factor receptor α (PDGFRα) is expressed by human HSCs, and PDGFRα expression is elevated in human liver disease. Using a green fluorescent protein (GFP) reporter mouse strain, we evaluated the role of PDGFRα in liver disease in mice and found that mouse HSCs express PDGFRα and expression is upregulated during carbon tetrachloride (CCl4) induced liver injury and fibrosis injection. This fibrotic response is reduced in Pdgfrα heterozygous mice, consistent with the hypothesis that liver fibrosis requires upregulation and activation of PDGFRα. These results indicate that Pdgfrα expression is important in the fibrotic response to liver injury in humans and mice, and suggest that blocking PDGFRα–specific signaling pathways in HSCs may provide therapeutic benefit for patients with chronic liver disease.
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影响因子：
2.9
作者：
Campbell, Jean S.;Johnson, Melissa M.;Fausto, Nelson
通讯作者：
Fausto, Nelson
DOI：
10.1073/pnas.0409722102
发表时间：
2005-03-01
影响因子：
11.1
作者：
Campbell, JS;Hughes, SD;Fausto, N
通讯作者：
Fausto, N
影响因子：
6.3
作者：
Ikura, Y;Morimoto, H;Sakurai, M
通讯作者：
Sakurai, M
影响因子：
5.3
作者：
Hamilton, TG;Klinghoffer, RA;Soriano, P
通讯作者：
Soriano, P
影响因子：
4
作者：
Chong, James J. H.;Reinecke, Hans;Murry, Charles E.
通讯作者：
Murry, Charles E.